Two birds with one stone: An antibiotic hit blocking Staphylococcus aureus heme uptake with serendipitous hemoglobin left-shifting activity
growth by targeting the hemophore-driven iron-acquisition system, highlighting its potential as an inhibitor and validating hemophores as antibacterial targets. Furthermore, for drug design purposes, we solved the X-ray structure of Hb:C35 complex. In contrast to the predicted binding pose, C35 binds tetrameric Hb in a cleft between the α subunits, stabilizing a relaxed conformation (R2) and increasing Hb oxygen affinity. This serendipitous result hints to C35 as a promising scaffold for developing compounds with diverse, or even dual, therapeutic aims, with antimicrobial and Hb-modulating activity.
Authors
- Marialaura Marchetti (ORCID: https://orcid.org/0000-0002-4615-6786)
- Francesco Marchesani (ORCID: https://orcid.org/0000-0003-4384-9015)
- Omar De Bei (ORCID: https://orcid.org/0000-0003-3916-8858)
- Loretta Lazzarato (ORCID: https://orcid.org/0000-0001-7100-8593)
- Emanuela Frangipani (ORCID: https://orcid.org/0000-0001-5619-7912)
- Somayeh Asghar Pour Hassan Kiyadeh (ORCID: https://orcid.org/0000-0001-7999-4762)
- Barbara Campanini (ORCID: https://orcid.org/0000-0003-0359-0627)
- Barbara Rolando (ORCID: https://orcid.org/0000-0001-6138-1503)
- Francesca Spyrakis (ORCID: https://orcid.org/0000-0002-4016-227X)
- Luca Ronda (ORCID: https://orcid.org/0000-0002-5389-2669)
- Sarah Hijazi (ORCID: https://orcid.org/0000-0002-0064-4610)
- Eleonora Gianquinto (ORCID: https://orcid.org/0000-0003-0996-5936)
- Serena Faggiano
- Stefano Bettati (ORCID: https://orcid.org/0000-0001-6787-0594)
- P. Brear (ORCID: https://orcid.org/0000-0002-4045-0474)
- Carlotta Compari (ORCID: https://orcid.org/0000-0002-4496-4472)
- Valeria Buoli Comani (ORCID: https://orcid.org/0000-0003-3115-2122)
Institutions
- University of Parma (IT)
- University of Urbino (IT)
- University of Cambridge (GB)
- National Research Council (IT)
- University of Turin (IT)
Publication Details
- Journal
- iScience
- Published
- 2026-04-07
- DOI
- https://doi.org/10.1016/j.isci.2026.115625
- Primary Topic
- Antimicrobial Resistance in Staphylococcus
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Università degli Studi di Torino
- Ministero dell'Istruzione e del Merito